We will assess the association between weight cycling and mortality among adult women in the Nurses' Health Study. During the past two decades some studies have reported that weight loss, weight variability, and weight cycling are associated with increased health risks. These reports of adverse health outcomes associated with weight cycling or loss have led some to question whether it is prudent to recommend that overweight adults should try to lose weight. Although most of the early studies found an increased risk of mortality or morbidity, the later studies have not been consistent. The discrepancy in results may reflect the fact that a variety of measures of weight cycling or weight variability have been used and some studies failed to differentiate intentional from unintentional weight loss. If unintentional weight loss carries a risk not associated with voluntary weight loss, a failure to account for the intentionality of the weight loss could potentially lead to faulty inference. We will assess the relationship between weight cycling and mortality among 77021 middle-aged and older women in the Nurses' Health Study who provided information on intentional weight losses in their adult life and survived for at least 2 years after completing the questions. We will evaluate whether independent of net weight gain during adulthood, which is known to increase risk of death, weight cycling is associated with an increased risk of mortality. We will assess the association of weight cycling due to intentional weight losses, as well as cycling due to unintentional weight losses. We will also assess whether weight variability, which includes both intentional and unintentional weight losses and gains, increase the mortality risk. Among the 77021 women eligible for the analysis, 4057 died during the following up, giving us excellent power to detect an association between weight cycling and mortality. We will examine whether weight status (i.e., being overweight or obese) or smoking status modifies any of these associations. If there is any evidence of effect modification, we will conduct stratified analyses. The combination of having large sample of adult women followed prospectively since 1976 as part of an ongoing cohort study, information on the intentionality of weight losses, and a sufficient number of deaths to have good power to identify predictors of mortality, provides us with a unique and valuable study design that will help to clarify the true nature of the association of weight cycling, weight variability, and mortality.